Alzheimer’s & Parkinson’s Disease

By: Dr. Atif Ali Bashir MD Pathology

Definition

•

Neurodegenerative disease

dementia.

is a condition which affects brain function. Neurodegenerative diseases result from deterioration of neurons. They are divided into two groups: – conditions causing problems with movements – conditions affecting memory and conditions related to – Examples: • Alzheimer’s • Parkinson’s • Huntington’s • Creutzfeldt-Jakob disease • Multiple Sclerosis • Amyotrophic Lateral Sclerosis (ALS or Lou Gehrig's Disease) – http://www.reference.com/browse/wiki/Neurodegenerative_di sease

Alzheimer’s Disease (AD)

An Understanding of Alzheimer’s Disease By Atif Ali Bashir

Alzheimer’s Disease

• Alzheimer’s disease (AD) is a devastating illness characterized by progressive memory loss, impaired thinking, personality change, and inability to perform routine tasks of daily living.

• The neural damage in AD is irreversible, and hence the disease cannot be cured.

• There is no effective drug for relieving symptoms, and no prospect of one in the near future.

[Auguste Deter, Alois Alzheimer's patient in November 1901, first described patient with Alzheimer's Disease.] [1864 - Dr. Alois Alzheimer, psychiatrist, pathologist, born in Marktbreit, Bavaria]

Prevalence of Neurodegenerative Diseases • 4-5 million people in the U.S. with Alzheimer’s disease (AD) – By 2050 this number is predicted to be 16 million • 1-1.5 million people in the U.S. with Parkinson’s Disease • Thousands with other NDs • 100,000 deaths/yr attributed to AD

What Causes AD?

• Age is the number one risk factor.

• A family history of having AD is another risk factor.

• Scientists don’t know exactly what causes the disease, and there is still a lot of research to be done.

• We do know that the main cause of brain cell death is an accumulation of the protein A-Beta.

• Once a brain cell dies it doesn’t come back, so AD causes a gradual loss of brain function.

Why do some people exposed to an environmental agents develop disease and others do not?

Poor Nutrition Genetics Other Diseases Environmental Toxins Obesity Development and Age Adverse Health Drugs Outcome

http://www.niehs.nih.gov/od/presentations/ppt/NIH-DHHS/PD-Schwartz-2006.ppt

Genetic and Environmental Factors in Alzheimer’s Disease Genes Susceptibility APOE-E



4 Probabilistic



-amyloid precursor Presenilin – 1 Presenilin – 2 Alzheimer ’s Disease

Slooter & Van Duijn, 1997

http://www.offordcentre.com/symposium/Merikangas.ppt#27

Environment Susceptibility Head trauma Vascular factors HSV-1 Total cholesterol Hypertension Protective N.S.A.I.D.

’s Estrogen Education

APP and PS families of proteins Familial Alzheimer disease is caused by mutations in at least 3 genes:

•

PSEN1 - Presenilin 1

– Mutations in this gene cause familial Alzheimer's type under 50 years old. (PSEN1 located on chromosome 14) – This protein has been identified as part of the enzymatic complex that cleaves amyloid beta peptide from APP.

•

PSEN2 - Presenilin 2

(PSEN2 located on chromosome 1) – The Presenilin 2 gene is very similar in structure and function to PSEN1. •

APP – Amyloid beta (A4) precursor protein

– Processing of the amyloid precursor protein – Mutations to the amyloid beta A4 precursor protein (APP) located on the long arm of chromosome 21 causes familial Alzheimer disease.

http://ibgwww.colorado.edu/~carey/p4102dir/slidesdir/HGSS_Chapter6_DCG.ppt

http://ibgwww.colorado.edu/~carey/p4102dir/slidesdir/HGSS_Chapter6_DCG.ppt

http://ibgwww.colorado.edu/~carey/p4102dir/slidesdir/HGSS_Chapter6_DCG.ppt http://www.upstate.com/features/app_lp.asp?c=221&r=556

Alzheimer’s disease: Gross and microscopic features

• •

Gross brain atrophy: neuronal loss Neuritic (senile) plaques

containing

B-amyloid

•

Neurofibrillary tangles

composed of phosphorylated microtubule associated

tau protein

•

Cerebral amyloidosis

Alzheimer’s Brain Control Brain

A Normal Brain and an AD Affected One

• In the normal brain there is a lot of healthy brain tissue in the language area. In the AD affected brain there is little in that area.

• There are many differences between the two brains including the memory, sulcus, gyrus, ventricle, and language areas. In the AD brain, these are either shrunken or stretched out to unhealthy measures.

Alzheimer’s disease: Clinical features

• Clinical features of dementia –

Impairment of recent memory

– Aphasia (naming), apraxia (motor), agnosia (object), executive functioning – Impaired level of function – Progressive over time – 47% of people over 85 years of age are affected

Advanced Symptoms

• As the disease progresses the symptoms are more easily noticed. • The AD patient might forget how to brush their teeth or comb their hair.

• They may not be able to think clearly and may fail to recognize familiar people or places.

• People with AD can become anxious or aggressive or wander away from home.

Parkinson's Disease

History

• James Parkinson • 1817, England • Shaking palsy • Paralysis agitans

Introduction

Parkinson’s disease is a chronic neurodegenerative

movement disorder

affecting voluntary and emotional movements and most commonly seen in the elderly, but is also found in the young and inexorably progresses leading to significant disability.

Epidemiology

• • • • • Primarily a disease of the elderly Mean age 55, Range 20 - 80 years Juvenile parkinsonism- Less than 20 years M/F = 3:2 Prevalence increases with age

Internal capsule Putamen Globus pallidus

Anatomy-Basal Ganglia

Caudate Nucleus

PATHOPHYSIOLOGY

PATHOPHYSIOLOGY

• SUBSTANTIA NIGRA GLOBUS, PARS RETICULATA DA A C H GABA STRIATUM CAUDATE, PUTAMEN

Chemical Balance in Corpus Striatum

 Excitatory Cholinergic pathway

BALANCE

 Inhibitory Dopaminergic pathway

Chemical Balance in Corpus Striatum

 Excitatory Cholinergic pathway

Imbalance

 Inhibitory Dopaminergic pathway

Parkinson’s disease Pathophysiology

Parkinson’s disease: Gross and microscopic findings

• Gross--

loss of pigment

in the

substantia nigra

• Microscopic--Lewy bodies with pigmented neuronal cell loss and gliosis – cortical Lewy bodies present in 80% or more of PD cases

Pathology - Lewy Bodies

 Eosinophilic hyaline inclusion bodies  Spherical dense hyaline core with a clear halo  Mechanism of formation unknown

Pathology

Lewy body dementia Parkinson ’s disease

Pathology-Parkinson’s disease

MIDBRAIN

Classification and Etiology

• Idiopathic Parkinson’s disease • Parkinson-like syndromes  Drug induced parkinsonism  Hypoxia  Tumor  Trauma  Vascular: Multiinfarct  Toxin: Mn, CO, MPTP and cyanide  Post-encephalitic parkinsonism (von Economo’s encephalitis)  Normal pressure hydrocephalus  Wilson’s disease, Huntington's disease

Clinical features of Idiopatic Parkinson’s disease.

Major features • Resting tremor in hands, arms, legs, jaw, and face • Bradykinesia • Rigidity- cogwheel or lead-pipe Minor features • Bradyphrenia • Speech abnormalities • Depression • Dysautonomia • Dystonia • Constipation • Hallucinations • Dysphagia

Parkinson’s disease Symptomatology

Posture  Kyphosis  Flexed elbows, knees and hips  Hands held in front of body  Trunk bent forward  Head bowed

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